期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 46, 期 3, 页码 560-569出版社
WILEY
DOI: 10.1002/eji.201545951
关键词
Antigen; Human T cells; MHC; Tetramers; Thymocytes
类别
资金
- Agence Nationale de la Recherche [ANR 11 BSV3 006 01]
- Ligue Contre le Cancer (Comite de Loire-Atlantique et du Maine et Loire)
- National Research Agency [ANR-11-LABX-0016-01, ANR-10-IBHU-005]
- Nantes Metropole
- Pays de la Loire Region
In the thymus, a T-cell repertoire able to confer protection against infectious and noninfectious agents in a peptide-dependent, self-MHC-restricted manner is selected. Direct detection of Ag-specific thymocytes, and analysis of the impact of the expression of the MHC-restricting allele on their frequency or function has never been studied in humans because of the extremely low precursor frequency. Here, we used a tetramer-based enrichment protocol to analyze the ex vivo frequency and activation-phenotype of human thymocytes specific for self, viral and tumor-antigens presented by HLA-A*0201 (A2) in individuals expressing or not this allele. Ag-specific thymocytes were quantified within both CD4CD8 double or single-positive compartments in every donor. Our data indicate that the maturation efficiency of Ag-specific thymocytes is poorly affected by HLA-A2 expression, in terms of frequencies. Nevertheless, A2-restricted T-cell lines from A2(+) donors reacted to A2(+) cell lines in a highly peptide-specific fashion, whereas their alloreactive counterparts showed off-target activity. This first ex vivo analysis of human antigen-specific thymocytes at different stages of human T-cell development should open new perspectives in the understanding of the human thymic selection process.
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